FIBER OUTGROWTH FROM ANTERIOR HYPOTHALAMIC AND CORTICAL XENOGRAFTS INTHE 3RD VENTRICLE

Fetal grafts of the anterior hypothalamus (SCN/AH) containing the supr achiasmatic nucleus (SCN) restore circadian rhythms to SCN-lesioned ho st hamsters and rats following implantation into the third ventricle. Previous studies suggest that intraventricular SCN/AH grafts are varia ble in their attachment sites, the extent of their outgrowth, and the precise targets innervated in the host brain. However, the use of diff erent methods to analyze graft outgrowth in this model has previously led to inconsistent results. We have reevaluated the outgrowth of feta l rat SCN/AH grafts implanted in the third ventricle of hamsters by us ing two methods: the carbocyanine dye, 1,1'dioctadecyl-3,3'-tetramethy lindocarbocyanine percholate (DiI), was placed directly onto grafted t issue; and a donor-specific neurofilament marker was used in conjuncti on with xenografts. We examined the specificity of outgrowth by compar ing SCN/AH xenografts with that of control cortical (CTX) xenografts. To evaluate whether SCN/AH graft efferents arise from the donor SCN, w e used micropunch grafts that contained minimal extra-SCN tissue. The results show that the use of a donor-specific neurofilament marker rev eals more extensive SCN/AH graft outgrowth than DiI. SCN/AH graft effe rents project into areas normally innervated by the intact SCN. Howeve r, this outgrowth is variable among graft recipients, is not specific to SCN/AH tissue, and does not necessarily derive from the donor SCN. The precise functional role of neural efferents arising from SCN/AH gr afts in the restoration of circadian clock function and the extent of SCN-derived efferents remain to be determined. (C) 1998 Wiley-Liss, In c.